Dendritic cells (DCs) are considered potent antigen-presenting cells (APCs), and are effective inducers of protective immunity against infectious diseases and cancer. These have prompted intense interest in the use of DCs as cellular vaccines; especially DCs differentiated form peripheral blood monocytes. However, clinical trials using DCs have only demonstrated very low rates of overall clinical response, highlighting the need to improve DC-based vaccines. Particular restrictions for the success of these cellular therapies have been the limited number of DCs that can be produced from monocytes, as DC cannot be expanded ex vivo, making it difficult to generate large numbers of these cells for use in long-term, multi-administration protocol. Moreover, DCs have a significant degree of variability in their ability to prime immune responses after cryopreservation. These limitations becomes especially important because greater DC numbers and treatments have been shown to elicit more robust antitumor immunity and improve clinical responses.
B cells represent a large pool of potent APCs, and are likely the only autologous APCs alternative to DC that can be generated ex vivo for immunotherapeutic purposes. While B cells have been described to induce T cell tolerance or even to block antitumor immune responses in vivo, these reports were restricted to resting B cells lacking important accessory and costimulatory molecules expression. On the other hand, B cells can be activated to become effective APCs by cells expressing CD40L in combination with cytokines or Toll-like receptor (TLR) ligands, however these approaches either did not induce optimal B cell activation (TLR ligands) or required the use of cell lines (CD40L), and these limitations make them unsuitable for clinical application.
Activated B cells have enhanced MHC and costimulatory molecules expression, and exhibit greatly improved antigen presentation capacity to fully activate naïve and memory T cells. Also of importance, activated B cells can recruit T cells through the secretion of chemokines and migrate to secondary lymphoid organs; critical requirements for in vivo induction of effective antitumor immune responses. Because B cells can be easily obtained ex vivo, they represent an attractive source of autologous APCs for immunotherapeutic applications. Moreover, activated B cells express MHC class I and II, and therefore be used with a wide range of antigens. Hence, a practical method that induces activation and proliferation of B cells is needed in the art to provide a cellular vaccine to target multiple types of tumors and infectious diseases.